In this proposal we will investigate the potential involvement of Lu. shannoni in the current transmission of visceral leishmaniasis (VL) to Foxhounds in the United States. The collaborative team assembled here include scientists with significant expertise required for this project, ranging from ecology and physiology of sand fly vectors, sand fly colonization experience and sand fly- Leishmania interaction, to mammalian host and parasite factors that lead to clinical disease outcome. The specific aims indicated in this proposal will be performed primarily by the vector biology laboratory of Dr. Marcelo Ramalho- Ortigao, at the Department of Entomology at Kansas State University, Manhattan, KS. The aims of this proposal are focused on the host organisms involved in the life cycle of Le. infantum, 1) the canine host and 2) the potential sand fly vector. Each aim will provide novel data, as well as complement findings in the other. In foci of sand fly-transmitted VL, a significant risk to humans is seen when Le. infantum-infected dogs are present. Thus, determining whether Lu. shannoni is indeed a suitable vector for Le. infantum in the United States is an important first step to sway state and federal health agencies towards the implementation of measures to control this severe vector-borne disease. Beyond the data to be generated with the studies proposed here, future studies will focus on potential differences underlying certain molecular aspects of Le. infantum circulating in South America and the strain currently involved in the infection of Foxhounds in the U.S. It will also serve on studies of sand fly population between potentially geographically separated populations of Lu. shannoni in North and South America. PUBLIC HEALTH RELEVANCE: Following the introduction of Leishmania infantum through importation of dogs from endemic areas, many entomologists believe that Lutzomyia shannoni, a native sand fly species, is playing a yet to be determined role in transmission of this parasite in the U.S. Lu. shannoni can take up parasites from an infected dog, but further parasite development within the sand fly has not been tested. CDC serological surveys indicate the current seroprevalence in U.S. Foxhounds is roughly 9%. A study of the emergence of visceral leishmaniasis in Israel indicated that a high prevalence of infected dogs (11.5%) as well as presence of a competent vector species led to the onset of disease in humans. As people and domestic canines would be at risk for visceral leishmaniasis should Lu. shannoni be a competent vector for this parasite, it is critical to determine whether domestic sand flies feed on dogs and/or humans and whether they are an effective vector for Le. infantum in the U.S.